{{Short description|Psychoactive stimulant and norepinephrine releasing agent}} {{Distinguish|Phenylalanine|DL-Phenylalanine}} {{Infobox drug | drug_name = | image = Phenylalaninol.svg | image_class = skin-invert-image | width = 225px | caption =
<!-- Clinical data --> | pronounce = | tradename = | Drugs.com = | MedlinePlus = | licence_CA = | licence_EU = | DailyMedID = | licence_US = | pregnancy_AU = | pregnancy_category = | dependency_liability = | addiction_liability = | routes_of_administration = | class = Psychostimulant; Norepinephrine releasing agent; Norepinephrine–dopamine releasing agent | ATC_prefix = | ATC_suffix =
<!-- Legal status --> | legal_status =
<!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion =
<!-- Identifiers --> | CAS_number = 16088-07-6 | CAS_supplemental = | PubChem = 76652 | PubChemSubstance = | IUPHAR_ligand = | DrugBank = | ChemSpiderID = 69116 | UNII = C8L8LX87R1 | KEGG = | ChEBI = | ChEMBL = 21676 | NIAID_ChemDB = | PDB_ligand = | synonyms = <small>DL</small>-Phenylalaninol; Phenylmethylethanolamine; Benzylethanolamine; <small>DL</small>-Phenylglycinol; α-(Hydroxymethyl)phenethylamine; PAL-329; PAL329
<!-- Chemical data --> | IUPAC_name = 2-amino-3-phenylpropan-1-ol | C=9 | H=13 | N=1 | O=1 | SMILES = C1=CC=C(C=C1)CC(CO)N | StdInChI = 1S/C9H13NO/c10-9(7-11)6-8-4-2-1-3-5-8/h1-5,9,11H,6-7,10H2 | StdInChIKey = STVVMTBJNDTZBF-UHFFFAOYSA-N }}
'''Phenylalaninol''' (code name '''PAL-329'''), or '''<small>DL</small>-phenylalaninol''', also known as '''phenylmethylethanolamine''' or as '''α-(hydroxymethyl)phenethylamine''', is a psychostimulant and monoamine releasing agent (MRA) of the phenethylamine family.<ref name="KohutJacobsRothman2017">{{cite journal | vauthors = Kohut SJ, Jacobs DS, Rothman RB, Partilla JS, Bergman J, Blough BE | title = Cocaine-like discriminative stimulus effects of "norepinephrine-preferring" monoamine releasers: time course and interaction studies in rhesus monkeys | journal = Psychopharmacology | volume = 234 | issue = 23–24 | pages = 3455–3465 | date = December 2017 | pmid = 28889212 | pmc = 5747253 | doi = 10.1007/s00213-017-4731-5 }}</ref><ref name="deMouraSherwoodPrisinzano2018">{{cite journal | vauthors = de Moura FB, Sherwood A, Prisinzano TE, Kohut SJ, Bergman J | title=Intravenous Self-Administration of Synthetic Cathinones in Rhesus Monkeys | journal=The FASEB Journal | volume=32 | issue=S1 | date=2018 | issn=0892-6638 | doi=10.1096/fasebj.2018.32.1_supplement.550.3 | page=| doi-access=free }}</ref> It is related to the amino acid phenylalanine and to the phenethylamine psychostimulants β-phenethylamine (phenylethylamine) and amphetamine (α-methylphenethylamine).<ref name="PubChem" />
Phenylalaninol is a psychostimulant and selective norepinephrine releasing agent (NRA) or norepinephrine-preferring norepinephrine–dopamine releasing agent (NDRA).<ref name="KohutJacobsRothman2017" /><ref name="deMouraSherwoodPrisinzano2018" /> The {{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}} values of phenylalaninol for monoamine release are 106{{nbsp}}nM for norepinephrine, 1,355{{nbsp}}nM for dopamine, and >10,000{{nbsp}}nM for serotonin in rat brain synaptosomes.<ref name="KohutJacobsRothman2017" /> It is dramatically less potent as an MRA than phenethylamine or amphetamine.<ref name="KohutJacobsRothman2017" /><ref name="Blough2008">{{cite book | vauthors = Blough B | chapter = Dopamine-releasing agents | veditors = Trudell ML, Izenwasser S | title = Dopamine Transporters: Chemistry, Biology and Pharmacology | pages = 305–320 | date = July 2008 | isbn = 978-0-470-11790-3 | oclc = 181862653 | ol = OL18589888W | publisher = Wiley | location = Hoboken [NJ] | doi = | url = https://books.google.com/books?id=QCagLAAACAAJ | chapter-url = https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf }}</ref> The potency of phenylalaninol in inducing norepinephrine release is 13-fold higher than its potency in inducing dopamine release.<ref name="KohutJacobsRothman2017" /> Similarly to other dopamine releasers like amphetamine, the drug shows cocaine-like effects and reinforcing properties in rhesus monkeys.<ref name="KohutJacobsRothman2017" /><ref name="deMouraSherwoodPrisinzano2018" /> The much greater potency of phenylalaninol in inducing norepinephrine over inducing dopamine release does not appear to interfere with its dopamine release-mediated reinforcing effects.<ref name="KohutJacobsRothman2017" /><ref name="deMouraSherwoodPrisinzano2018" />
The clinically used stimulant, wakefulness-promoting agent, and well-balanced norepinephrine–dopamine reuptake inhibitor (NDRI) solriamfetol (brand name Sunosi; ''O''-carbamoyl-<small>D</small>-phenylalaninol) is a derivative of phenylalaninol with a carbamoyl substitution at the hydroxyl group of the molecule.<ref name="YangGao2019">{{cite journal | vauthors = Yang J, Gao J | title = Solriamfetol for the treatment of excessive daytime sleepiness associated with narcolepsy | journal = Expert Rev Clin Pharmacol | volume = 12 | issue = 8 | pages = 723–728 | date = August 2019 | pmid = 31215815 | doi = 10.1080/17512433.2019.1632705 | url = }}</ref> Phenylalaninol is a known impurity in chemical synthesis of solriamfetol.<ref name="FejősTóthVárnai2021">{{cite journal | vauthors = Fejős I, Tóth G, Várnai B, Szabó ZI, Köteles I, Malanga M, Béni S | title = Enantioseparation of solriamfetol and its major impurity phenylalaninol by capillary electrophoresis using sulfated gamma cyclodextrin | journal = Electrophoresis | volume = 42 | issue = 17–18 | pages = 1818–1825 | date = September 2021 | pmid = 34109644 | doi = 10.1002/elps.202100076 | url = | doi-access = free }}</ref>
The predicted log P of phenylalaninol is 0.7 to 0.77 and hence it is relatively hydrophilic.<ref name="PubChem">{{cite web | title=DL-Phenylalaninol | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/76652 | access-date=15 January 2025}}</ref><ref name="ChemSpider">{{cite web | title=phenylalaninol | website=ChemSpider | date=10 June 2024 | url=https://www.chemspider.com/Chemical-Structure.69116.html | access-date=15 January 2025}}</ref> The compound appears to be actively transported in the body by some of the same transporters that transport phenylalanine, such as LAT3.<ref name="ShimomuraFukushimaDanno1975">{{cite journal | vauthors = Shimomura K, Fukushima T, Danno T, Matsumoto K, Miyoshi M | title = Inhibition of intestinal absorption of phenylalanine by phenylalaninol | journal = J Biochem | volume = 78 | issue = 2 | pages = 269–275 | date = August 1975 | pmid = 1228171 | doi = 10.1093/oxfordjournals.jbchem.a130904 | url = }}</ref><ref name="BabuKanaiChairoungdua2003">{{cite journal | vauthors = Babu E, Kanai Y, Chairoungdua A, Kim DK, Iribe Y, Tangtrongsup S, Jutabha P, Li Y, Ahmed N, Sakamoto S, Anzai N, Nagamori S, Endou H | title = Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters | journal = J Biol Chem | volume = 278 | issue = 44 | pages = 43838–45 | date = October 2003 | pmid = 12930836 | doi = 10.1074/jbc.M305221200 | doi-access = free | url = }}</ref>
==References== {{Reflist}}
{{Stimulants}} {{Monoamine releasing agents}} {{Phenethylamines}}
Category:Alcohols Category:Norepinephrine-dopamine releasing agents Category:Norepinephrine releasing agents Category:Stimulants Category:Substituted amphetamines
{{Psychoactive-stub}}